Predicting circRNA-RBP interaction sites using a codon-based encoding and hybrid deep neural networks

AbstractCircular RNAs (circRNAs), with their crucial roles in gene regulation and disease development, have become a rising star in the RNA world. A lot of previous wet-lab studies focused on the interaction mechanisms between circRNAs and RNA-binding proteins (RBPs), as the knowledge of circRNA-RBP association is very important for understanding functions of circRNAs. Recently, the abundant CLIP-Seq experimental data has made the large-scale identification and analysis of circRNA-RBP interactions possible, while no computational tool based on machine learning has been developed yet.We present a new deep learning-based method, CRIP (CircRNAs Interact with Proteins), for the prediction of RBP binding sites on circRNAs, using only the RNA sequences. In order to fully exploit the sequence information, we propose a stacked codon-based encoding scheme and a hybrid deep learning architecture, in which a convolutional neural network (CNN) learns high-level abstract features and a recurrent neural network (RNN) learns long dependency in the sequences. We construct 37 datasets including sequence fragments of binding sites on circRNAs, and each set corresponds to one RBP. The experimental results show that the new encoding scheme is superior to the existing feature representation methods for RNA sequences, and the hybrid network outperforms conventional classifiers by a large margin, where both the CNN and RNN components contribute to the performance improvement. To the best of our knowledge, CRIP is the first machine learning-based tool specialized in the prediction of circRNA-RBP interactions, which is expected to play an important role for large-scale function analysis of circRNAs.

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Multi-resBind: a residual network-based multi-label classifier for in vivo RNA binding prediction and preference visualization

BMC Bioinformatics ◽

10.1186/s12859-021-04430-y ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Shitao Zhao ◽

Michiaki Hamada

Keyword(s):

Neural Network ◽

Deep Learning ◽

Binding Sites ◽

Prediction Accuracy ◽

Large Scale ◽

Rna Binding ◽

Binding Prediction ◽

Binding Preference ◽

The Impact

Abstract Background Protein-RNA interactions play key roles in many processes regulating gene expression. To understand the underlying binding preference, ultraviolet cross-linking and immunoprecipitation (CLIP)-based methods have been used to identify the binding sites for hundreds of RNA-binding proteins (RBPs) in vivo. Using these large-scale experimental data to infer RNA binding preference and predict missing binding sites has become a great challenge. Some existing deep-learning models have demonstrated high prediction accuracy for individual RBPs. However, it remains difficult to avoid significant bias due to the experimental protocol. The DeepRiPe method was recently developed to solve this problem via introducing multi-task or multi-label learning into this field. However, this method has not reached an ideal level of prediction power due to the weak neural network architecture. Results Compared to the DeepRiPe approach, our Multi-resBind method demonstrated substantial improvements using the same large-scale PAR-CLIP dataset with respect to an increase in the area under the receiver operating characteristic curve and average precision. We conducted extensive experiments to evaluate the impact of various types of input data on the final prediction accuracy. The same approach was used to evaluate the effect of loss functions. Finally, a modified integrated gradient was employed to generate attribution maps. The patterns disentangled from relative contributions according to context offer biological insights into the underlying mechanism of protein-RNA interactions. Conclusions Here, we propose Multi-resBind as a new multi-label deep-learning approach to infer protein-RNA binding preferences and predict novel interactions. The results clearly demonstrate that Multi-resBind is a promising tool to predict unknown binding sites in vivo and gain biology insights into why the neural network makes a given prediction.

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RPITER: A Hierarchical Deep Learning Framework for ncRNA–Protein Interaction Prediction

International Journal of Molecular Sciences ◽

10.3390/ijms20051070 ◽

2019 ◽

Vol 20 (5) ◽

pp. 1070 ◽

Cited By ~ 12

Author(s):

Cheng Peng ◽

Siyu Han ◽

Hui Zhang ◽

Ying Li

Keyword(s):

Neural Network ◽

Deep Learning ◽

Protein Interaction ◽

Rna Binding ◽

Prediction Models ◽

Rna Binding Proteins ◽

Biological Research ◽

Sequence Information ◽

Learning Framework ◽

Coding Method

Non-coding RNAs (ncRNAs) play crucial roles in multiple fundamental biological processes, such as post-transcriptional gene regulation, and are implicated in many complex human diseases. Mostly ncRNAs function by interacting with corresponding RNA-binding proteins. The research on ncRNA–protein interaction is the key to understanding the function of ncRNA. However, the biological experiment techniques for identifying RNA–protein interactions (RPIs) are currently still expensive and time-consuming. Due to the complex molecular mechanism of ncRNA–protein interaction and the lack of conservation for ncRNA, especially for long ncRNA (lncRNA), the prediction of ncRNA–protein interaction is still a challenge. Deep learning-based models have become the state-of-the-art in a range of biological sequence analysis problems due to their strong power of feature learning. In this study, we proposed a hierarchical deep learning framework RPITER to predict RNA–protein interaction. For sequence coding, we improved the conjoint triad feature (CTF) coding method by complementing more primary sequence information and adding sequence structure information. For model design, RPITER employed two basic neural network architectures of convolution neural network (CNN) and stacked auto-encoder (SAE). Comprehensive experiments were performed on five benchmark datasets from PDB and NPInter databases to analyze and compare the performances of different sequence coding methods and prediction models. We found that CNN and SAE deep learning architectures have powerful fitting abilities for the k-mer features of RNA and protein sequence. The improved CTF coding method showed performance gain compared with the original CTF method. Moreover, our designed RPITER performed well in predicting RNA–protein interaction (RPI) and could outperform most of the previous methods. On five widely used RPI datasets, RPI369, RPI488, RPI1807, RPI2241 and NPInter, RPITER obtained A U C of 0.821, 0.911, 0.990, 0.957 and 0.985, respectively. The proposed RPITER could be a complementary method for predicting RPI and constructing RPI network, which would help push forward the related biological research on ncRNAs and lncRNAs.

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Anti-CRISPR RNAs: designing universal riboregulators with deep learning of Csy4-mediated RNA processing

10.1101/2020.11.15.384107 ◽

2020 ◽

Author(s):

Haotian Guo ◽

Xiaohu Song ◽

Ariel B. Lindner

Keyword(s):

Neural Network ◽

Machine Learning ◽

Deep Learning ◽

Rna Processing ◽

Binding Sites ◽

Transcriptional Networks ◽

Promising Alternative ◽

Wide Range ◽

Flanking Sequences ◽

Structural Commonality

AbstractRNA-based regulation offers a promising alternative of protein-based transcriptional networks. However, designing synthetic riboregulators with desirable functionalities using arbitrary sequences remains challenging, due in part to insufficient exploration of RNA sequence-to-function landscapes. Here we report that CRISPR-Csy4 mediates a nearly all-or-none processing of precursor CRISPR RNAs (pre-crRNAs), by profiling Csy4 binding sites flanked by > 1 million random sequences. This represents an ideal sequence-to-function space for universal riboregulator designs. Lacking discernible sequence-structural commonality among processable pre-crRNAs, we trained a neural network for accurate classification (f1-score ≈ 0.93). Inspired by exhaustive probing of palindromic flanking sequences, we designed anti-CRISPR RNAs (acrRNAs) that suppress processing of pre-crRNAs via stem stacking. We validated machine-learning-guided designs with >30 functional pairs of acrRNAs and pre-crRNAs to achieve switch-like properties. This opens a wide range of plug-and-play applications tailored through pre-crRNA designs, and represents a programmable alternative to protein-based anti-CRISPRs.

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Prediction of RNA-protein sequence and structure binding preferences using deep convolutional and recurrent neural networks

10.1101/146175 ◽

2017 ◽

Cited By ~ 3

Author(s):

Xiaoyong Pan ◽

Peter Rijnbeek ◽

Junchi Yan ◽

Hong-Bin Shen

Keyword(s):

Neural Networks ◽

Binding Sites ◽

Large Scale ◽

Rna Binding ◽

Short Term Memory ◽

Rna Binding Proteins ◽

Point Of View ◽

Rna Sequences ◽

Close Relationship ◽

Binding Sequence

AbstractRNA regulation is significantly dependent on its binding protein partner, which is known as the RNA-binding proteins (RBPs). Unfortunately, the binding preferences for most RBPs are still not well characterized, especially on the structure point of view. Informative signals hiding and interdependencies between sequence and structure specificities are two challenging problems for both predicting RBP binding sites and accurate sequence and structure motifs mining.In this study, we propose a deep learning-based method, iDeepS, to simultaneously identify the binding sequence and structure motifs from RNA sequences using convolutional neural networks (CNNs) and a bidirectional long short term memory network (BLSTM). We first perform one-hot encoding for both the sequence and predicted secondary structure, which are appropriate for subsequent convolution operations. To reveal the hidden binding knowledge from the observations, the CNNs are applied to learn the abstract motif features. Considering the close relationship between sequences and predicted structures, we use the BLSTM to capture the long range dependencies between binding sequence and structure motifs identified by the CNNs. Finally, the learned weighted representations are fed into a classification layer to predict the RBP binding sites. We evaluated iDeepS on verified RBP binding sites derived from large-scale representative CLIP-seq datasets, and the results demonstrate that iDeepS can reliably predict the RBP binding sites on RNAs, and outperforms the state-of-the-art methods. An important advantage is that iDeepS is able to automatically extract both binding sequence and structure motifs, which will improve our transparent understanding of the mechanisms of binding specificities of RBPs. iDeepS is available at https://github.com/xypan1232/iDeepS.

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Deep neural networks for inferring binding sites of RNA-binding proteins by using distributed representations of RNA primary sequence and secondary structure

BMC Genomics ◽

10.1186/s12864-020-07239-w ◽

2020 ◽

Vol 21 (S13) ◽

Author(s):

Lei Deng ◽

Youzhi Liu ◽

Yechuan Shi ◽

Wenhao Zhang ◽

Chun Yang ◽

...

Keyword(s):

Neural Networks ◽

Secondary Structure ◽

Binding Sites ◽

Large Scale ◽

Binding Proteins ◽

Rna Binding ◽

Rna Binding Proteins ◽

Secondary Structures ◽

Rna Sequences ◽

Distributed Representations

Abstract Background RNA binding proteins (RBPs) play a vital role in post-transcriptional processes in all eukaryotes, such as splicing regulation, mRNA transport, and modulation of mRNA translation and decay. The identification of RBP binding sites is a crucial step in understanding the biological mechanism of post-transcriptional gene regulation. However, the determination of RBP binding sites on a large scale is a challenging task due to high cost of biochemical assays. Quite a number of studies have exploited machine learning methods to predict binding sites. Especially, deep learning is increasingly used in the bioinformatics field by virtue of its ability to learn generalized representations from DNA and protein sequences. Results In this paper, we implemented a novel deep neural network model, DeepRKE, which combines primary RNA sequence and secondary structure information to effectively predict RBP binding sites. Specifically, we used word embedding algorithm to extract features of RNA sequences and secondary structures, i.e., distributed representation of k-mers sequence rather than traditional one-hot encoding. The distributed representations are taken as input of convolutional neural networks (CNN) and bidirectional long-term short-term memory networks (BiLSTM) to identify RBP binding sites. Our results show that deepRKE outperforms existing counterpart methods on two large-scale benchmark datasets. Conclusions Our extensive experimental results show that DeepRKE is an efficacious tool for predicting RBP binding sites. The distributed representations of RNA sequences and secondary structures can effectively detect the latent relationship and similarity between k-mers, and thus improve the predictive performance. The source code of DeepRKE is available at https://github.com/youzhiliu/DeepRKE/.

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Machine Learning with ROOT/TMVA

EPJ Web of Conferences ◽

10.1051/epjconf/202024506019 ◽

2020 ◽

Vol 245 ◽

pp. 06019

Author(s):

Kim Albertsson ◽

Sitong An ◽

Sergei Gleyzer ◽

Lorenzo Moneta ◽

Joana Niermann ◽

...

Keyword(s):

Neural Network ◽

Machine Learning ◽

Deep Learning ◽

Large Scale ◽

Learning Tools ◽

Learning Models ◽

New Developments ◽

Training Time ◽

Future Developments ◽

Machine Learning Models

ROOT provides, through TMVA, machine learning tools for data analysis at HEP experiments and beyond. We present recently included features in TMVA and the strategy for future developments in the diversified machine learning landscape. Focus is put on fast machine learning inference, which enables analysts to deploy their machine learning models rapidly on large scale datasets. The new developments are paired with newly designed C++ and Python interfaces supporting modern C++ paradigms and full interoperability in the Python ecosystem. We present as well a new deep learning implementation for convolutional neural network using the cuDNN library for GPU. We show benchmarking results in term of training time and inference time, when comparing with other machine learning libraries such as Keras/Tensorflow.

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RNA-protein binding motifs mining with a new hybrid deep learning based cross-domain knowledge integration approach

10.1101/085191 ◽

2016 ◽

Cited By ~ 2

Author(s):

Xiaoyong Pan ◽

Hong-Bin Shen

Keyword(s):

Neural Network ◽

Deep Learning ◽

Binding Sites ◽

Domain Knowledge ◽

Large Scale ◽

Knowledge Integration ◽

State Of The Art ◽

Binding Motifs ◽

Abstraction Level ◽

Cross Domain

AbstractBackgroundRNAs play key roles in cells through the interactions with proteins known as the RNA-binding proteins (RBP) and their binding motifs enable crucial understanding of the post-transcriptional regulation of RNAs. How the RBPs correctly recognize the target RNAs and why they bind specific positions is still far from clear. Machine learning-based algorithms are widely acknowledged to be capable of speeding up this process. Although many automatic tools have been developed to predict the RNA-protein binding sites from the rapidly growing multi-resource data, e.g. sequence, structure, their domain specific features and formats have posed significant computational challenges. One of current difficulties is that the cross-source shared common knowledge is at a higher abstraction level beyond the observed data, resulting in a low efficiency of direct integration of observed data across domains. The other difficulty is how to interpret the prediction results. Existing approaches tend to terminate after outputting the potential discrete binding sites on the sequences, but how to assemble them into the meaningful binding motifs is a topic worth of further investigation.ResultsIn viewing of these challenges, we propose a deep learning-based framework (iDeep) by using a novel hybrid convolutional neural network and deep belief network to predict the RBP interaction sites and motifs on RNAs. This new protocol is featured by transforming the original observed data into a high-level abstraction feature space using multiple layers of learning blocks, where the shared representations across different domains are integrated. To validate our iDeep method, we performed experiments on 31 large-scale CLIP-seq datasets, and our results show that by integrating multiple sources of data, the average AUC can be improved by 8% compared to the best single-source-based predictor; and through cross-domain knowledge integration at an abstraction level, it outperforms the state-of-the-art predictors by 6%. Besides the overall enhanced prediction performance, the convolutional neural network module embedded in iDeep is also able to automatically capture the interpretable binding motifs for RBPs. Large-scale experiments demonstrate that these mined binding motifs agree well with the experimentally verified results, suggesting iDeep is a promising approach in the real-world applications.ConclusionThe iDeep framework not only can achieve promising performance than the state-of-the-art predictors, but also easily capture interpretable binding motifs. iDeep is available at http://www.csbio.sjtu.edu.cn/bioinf/iDeep

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A State-of-the-Art Survey on Deep Learning Theory and Architectures

Electronics ◽

10.3390/electronics8030292 ◽

2019 ◽

Vol 8 (3) ◽

pp. 292 ◽

Cited By ~ 157

Author(s):

Md Zahangir Alom ◽

Tarek M. Taha ◽

Chris Yakopcic ◽

Stefan Westberg ◽

Paheding Sidike ◽

...

Keyword(s):

Neural Network ◽

Machine Learning ◽

Deep Learning ◽

Reinforcement Learning ◽

Language Processing ◽

Large Scale ◽

Medical Information ◽

State Of The Art ◽

Generative Models ◽

Learning Approaches

In recent years, deep learning has garnered tremendous success in a variety of application domains. This new field of machine learning has been growing rapidly and has been applied to most traditional application domains, as well as some new areas that present more opportunities. Different methods have been proposed based on different categories of learning, including supervised, semi-supervised, and un-supervised learning. Experimental results show state-of-the-art performance using deep learning when compared to traditional machine learning approaches in the fields of image processing, computer vision, speech recognition, machine translation, art, medical imaging, medical information processing, robotics and control, bioinformatics, natural language processing, cybersecurity, and many others. This survey presents a brief survey on the advances that have occurred in the area of Deep Learning (DL), starting with the Deep Neural Network (DNN). The survey goes on to cover Convolutional Neural Network (CNN), Recurrent Neural Network (RNN), including Long Short-Term Memory (LSTM) and Gated Recurrent Units (GRU), Auto-Encoder (AE), Deep Belief Network (DBN), Generative Adversarial Network (GAN), and Deep Reinforcement Learning (DRL). Additionally, we have discussed recent developments, such as advanced variant DL techniques based on these DL approaches. This work considers most of the papers published after 2012 from when the history of deep learning began. Furthermore, DL approaches that have been explored and evaluated in different application domains are also included in this survey. We also included recently developed frameworks, SDKs, and benchmark datasets that are used for implementing and evaluating deep learning approaches. There are some surveys that have been published on DL using neural networks and a survey on Reinforcement Learning (RL). However, those papers have not discussed individual advanced techniques for training large-scale deep learning models and the recently developed method of generative models.

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DeCban: Prediction of circRNA-RBP Interaction Sites by Using Double Embeddings and Cross-Branch Attention Networks

Frontiers in Genetics ◽

10.3389/fgene.2020.632861 ◽

2021 ◽

Vol 11 ◽

Author(s):

Liangliang Yuan ◽

Yang Yang

Keyword(s):

Deep Learning ◽

Protein Interactions ◽

Rna Binding ◽

Rna Binding Proteins ◽

Rna World ◽

Circular Rnas ◽

Rna Sequences ◽

Attention Model ◽

Interaction Sites ◽

The Cross

Circular RNAs (circRNAs), as a rising star in the RNA world, play important roles in various biological processes. Understanding the interactions between circRNAs and RNA binding proteins (RBPs) can help reveal the functions of circRNAs. For the past decade, the emergence of high-throughput experimental data, like CLIP-Seq, has made the computational identification of RNA-protein interactions (RPIs) possible based on machine learning methods. However, as the underlying mechanisms of RPIs have not been fully understood yet and the information sources of circRNAs are limited, the computational tools for predicting circRNA-RBP interactions have been very few. In this study, we propose a deep learning method to identify circRNA-RBP interactions, called DeCban, which is featured by hybrid double embeddings for representing RNA sequences and a cross-branch attention neural network for classification. To capture more information from RNA sequences, the double embeddings include pre-trained embedding vectors for both RNA segments and their converted amino acids. Meanwhile, the cross-branch attention network aims to address the learning of very long sequences by integrating features of different scales and focusing on important information. The experimental results on 37 benchmark datasets show that both double embeddings and the cross-branch attention model contribute to the improvement of performance. DeCban outperforms the mainstream deep learning-based methods on not only prediction accuracy but also computational efficiency. The data sets and source code of this study are freely available at: https://github.com/AaronYll/DECban.

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Identifikasi Foto Wanita Berhijab dari Majalah Untuk Pembuatan Katalog Busana Muslim Otomatis Memanfaatkan Convolutional Neural Network

Journal of Intelligent System and Computation ◽

10.52985/insyst.v1i2.87 ◽

2019 ◽

Vol 1 (2) ◽

pp. 85-91

Author(s):

M. Najamudin Ridha ◽

Endang Setyati ◽

Yosi Kristian

Keyword(s):

Neural Network ◽

Machine Learning ◽

Deep Learning ◽

Convolutional Neural Network ◽

Image Classification ◽

Large Scale ◽

Data Augmentation ◽

Rectified Linear Unit

Abstrak—Perkembangan Fashion Muslim di Indonesia terus meningkat, disisi lain terobosan baru pada Deep Learning dengan memadukan arsitektur seperti dropout regularizations dan Rectified Linear Unit (ReLU) sebagai fungsi aktivasi dan data augmentation, mampu mencapai terobosan pada large scale image classification. Penelitian ini menggunakan metode deteksi objek wajah dengan Haar Cascades Classification untuk mendapatkan sample dataset wajah dan preprocessing data testing untuk dilanjutkan pada metode machine learning untuk klasifikasi citra dengan Convolutional Neural Network. Dataset yang digunakan adalah kumpulan katalog busana online, dataset yang sudah di preprocessing dibagi menjadi dua kategori, yaitu Hijab untuk semua citra wanita berhijab, dan Non Hijab untuk citra yang bukan wanita berhijab. selanjutnya klasifikasi citra menggunakan data ujicoba majalah digital terbitan Hijabella, Joy Indonesia dan Scarf Indonesia. Semakin besar resolusi citra input untuk preprocessing pada majalah digital, maka akan semakin banyak objek citra yang terdeteksi, dengan meningkatkan jumlah dataset untuk training dan validasi, mampu menambah hasil akurasi yang didapatkan, terjadi peningkatan akurasi pada dataset 2.500 wajah perkategori ke 5.000 wajah perkategori dengan resolusi 720p meningkat dari rata-rata 81.30% menjadi 82.31%, peningkatan rata-rata 1.01% dan tertinggi 2.14%, sedangkan resolusi 1080p meningkat dari rata-rata 83.03% menjadi 83.68%, peningkatan rata-rata 0.65% dan tertinggi 1.73%, akurasi tertinggi adalah sebesar 84.72% menggunakan model dataset 5.000 secara acak perkategori.

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